Infections of the urinary tract appear to develop primarily in a retrograde manner, with the rectal flora being the usual source of pathogens. A step-wise colonization proceding from rectum to vagina to urethra has been demonstrated prior to the onset of infection. Antibacterial defense mechanisms of the vagina, urethra, and bladder thus represent the first line of defense against lower urinary tract infection and pyelonephritis. The bladder defense mechanisms include: 1. the mechanical washing action of urine flow, 2. antibacterial properties of urine, and 3. antibacterial activity to the vesical mucosa. Voiding is extremely important in ridding the bladder of small numbers of the urethral microorganisms. Infection occurs when these organisms become attached to the bladder wall and remain there after voiding to reseed fresh urine. A substance that could prevent bacteria from binding to the bladder mucosa would be a valuable antibacterial defense mechanism. We have developed a reliable and reproducible model for quantitatively measuring bacterial adsorption to the bladder mucosa and have shown that the bladder produces one or more substances that prevent bacterial attachment. Bacteria bound poorly to the normal vesical mucosa, but after a short acid treatment mucosa had totally recovered its resistance to bacterial binding, suggesting that the inhibitory mechanism is secretory in nature. Histochemical studies demonstrated a loss of surface mucopolysaccharides corresponding to the deficiency in the bladder's ability to resist bacterial binding, This suggest that the primary antibacterial defense of the bladder may be surface mucopolysaccharides. Our proposed research project includes: 1. a study of the kinetics of vesical mucosa - bacteria interaction, 2. histochemical studies (light and electron microscopy) of the bladder surface, and 3. isolation of substances that protect the bladder from bacterial adsorption.